dc.contributor.author | Nuñez Viadero, Eider | |
dc.contributor.author | Jones, Frederick | |
dc.contributor.author | Muguruza Montero, Arantza | |
dc.contributor.author | Urrutia Iñiguez, Janire | |
dc.contributor.author | Aguado Martínez, Alejandra | |
dc.contributor.author | Malo de la Fuente, Covadonga | |
dc.contributor.author | Bernardo Seisdedos, Ganeko | |
dc.contributor.author | Domene, Carmen | |
dc.contributor.author | Millet Aguilar-Galindo, Oscar | |
dc.contributor.author | Gamper, Nikita | |
dc.contributor.author | Villarroel Muñoz, Álvaro | |
dc.date.accessioned | 2023-04-21T16:38:33Z | |
dc.date.available | 2023-04-21T16:38:33Z | |
dc.date.issued | 2023-01 | |
dc.identifier.citation | eLife 12 : (2023) // Article ID e81961 | es_ES |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | http://hdl.handle.net/10810/60885 | |
dc.description.abstract | Neuronal KV7 channels, important regulators of cell excitability, are among the most sensitive proteins to reactive oxygen species. The S2S3 linker of the voltage sensor was reported as a site-mediating redox modulation of the channels. Recent structural insights reveal potential interactions between this linker and the Ca2+-binding loop of the third EF-hand of calmodulin (CaM), which embraces an antiparallel fork formed by the C-terminal helices A and B, constituting the calcium responsive domain (CRD). We found that precluding Ca2+ binding to the EF3 hand, but not to EF1, EF2, or EF4 hands, abolishes oxidation-induced enhancement of KV7.4 currents. Monitoring FRET (Fluorescence Resonance Energy Transfer) between helices A and B using purified CRDs tagged with fluorescent proteins, we observed that S2S3 peptides cause a reversal of the signal in the presence of Ca2+ but have no effect in the absence of this cation or if the peptide is oxidized. The capacity of loading EF3 with Ca2+ is essential for this reversal of the FRET signal, whereas the consequences of obliterating Ca2+ binding to EF1, EF2, or EF4 are negligible. Furthermore, we show that EF3 is critical for translating Ca2+ signals to reorient the AB fork. Our data are consistent with the proposal that oxidation of cysteine residues in the S2S3 loop relieves KV7 channels from a constitutive inhibition imposed by interactions between the EF3 hand of CaM which is crucial for this signaling. | es_ES |
dc.description.sponsorship | Ministerio de Ciencia e Innovacion PID2021-128286NB-100Wellcome Trust 212302/Z/18/ZMedical Research Centre MR/P015727/1Eusko Jaurlaritza IT1707-22 Ekonomiaren Garapen eta Lehiakortasun Saila, Eusko Jaurlaritza BG2019Ministerio de Ciencia e Innovacion RTI2018-097839-B-100Ministerio de Ciencia e Innovacion RTI2018-101269-B-I00Eusko Jaurlaritza IT1165-19 Ekonomiaren Garapen eta Lehiakortasun Saila,Eusko Jaurlaritza KK-2020/00110Eusko Jaurlaritza PRE_2018-2_0082Eusko Jaurlaritza POS_2021_1_0017Eusko Jaurlaritza PRE_2018-2_0126 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | eLife Sciences | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2021-128286NB-100 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018‐097839-B-100 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-101269-B-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | KCNQ | es_ES |
dc.subject | calmodulin | es_ES |
dc.subject | redox | es_ES |
dc.subject | calcium | es_ES |
dc.subject | EF-hand | es_ES |
dc.subject | signal transduction | es_ES |
dc.subject | E | es_ES |
dc.subject | coli | es_ES |
dc.title | Redox regulation of KV7 channels through EF3 hand of calmodulin | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | Copyright Nuñez et al. This
article is distributed under the
terms of the Creative Commons
Attribution License, which
permits unrestricted use and
redistribution provided that the
original author and source are
credited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://elifesciences.org/articles/81961 | es_ES |
dc.identifier.doi | 10.7554/eLife.81961 | |
dc.departamentoes | Fisiología | es_ES |
dc.departamentoes | Física aplicada I | es_ES |
dc.departamentoeu | Fisika aplikatua I | es_ES |
dc.departamentoeu | Fisiologia | es_ES |